2,179 results match your criteria: "Li Ka-Shing Centre[Affiliation]"
Genes Dev
December 2024
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, United Kingdom
The gene-regulatory mechanisms controlling the expression of the germline PIWI-interacting RNA (piRNA) pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. Here, using as a model, we combined multiple genomics approaches to reveal the transcription factor Ovo as regulator of the germline piRNA pathway in ovarian germ cells.
View Article and Find Full Text PDFNature
January 2025
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.
View Article and Find Full Text PDFPLoS Genet
January 2025
Melbourne Integrative Genomics, School of Mathematics & Statistics, University of Melbourne, Victoria, Australia.
Inference of evolutionary and demographic parameters from a sample of genome sequences often proceeds by first inferring identical-by-descent (IBD) genome segments. By exploiting efficient data encoding based on the ancestral recombination graph (ARG), we obtain three major advantages over current approaches: (i) no need to impose a length threshold on IBD segments, (ii) IBD can be defined without the hard-to-verify requirement of no recombination, and (iii) computation time can be reduced with little loss of statistical efficiency using only the IBD segments from a set of sequence pairs that scales linearly with sample size. We first demonstrate powerful inferences when true IBD information is available from simulated data.
View Article and Find Full Text PDFJ Pathol
February 2025
Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland.
Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.
View Article and Find Full Text PDFInflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms.
View Article and Find Full Text PDFEnviron Int
December 2024
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Cancer Rep (Hoboken)
December 2024
International Agency for Research on Cancer, Lyon, France.
Background: Oesophageal cancer is a public health concern in Ethiopia. Identifying the incidence and demographic profile of the two histological subtypes: oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC) are the key steps in recognizing the disease burden and potential aetiopathological associations.
Aim: The aim of this study is to identify the age and gender-specific incidence patterns of the most common subtype of oesophageal cancer in a high-incidence area of Ethiopia.
Transl Stroke Res
December 2024
Department of Psychology, Faculty of Science, University of Alberta, P217 Biological Sciences Bldg, Edmonton, AB, Canada.
Intracerebral hemorrhage (ICH) along with aggravating factors, such as edema, can raise intracranial pressure (ICP) to pathological levels. Diversion of some cerebrospinal fluid (CSF) and venous blood out of the cranium can limit ICP rises while maintaining cerebral perfusion pressure. Brain tissue itself is widely considered immutable in volume but prone to distortion (e.
View Article and Find Full Text PDFCommun Biol
December 2024
BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.
View Article and Find Full Text PDFOncogene
December 2024
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
PLoS Biol
December 2024
Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
To keep ahead of the evolution of resistance to insecticides in mosquitoes, national malaria control programmes must make use of a range of insecticides, both old and new, while monitoring resistance mechanisms. The outdoor-biting malaria vector Anopheles arabiensis is of increasing concern for malaria transmission because it is apparently less susceptible to many indoor control interventions, yet knowledge of its mechanisms of resistance remains limited. Furthermore, comparatively little is known in general about resistance to non-pyrethroid insecticides such as pirimiphos-methyl (PM), which are crucial for effective control in the context of globally high resistance to pyrethroids.
View Article and Find Full Text PDFDiagnostics (Basel)
November 2024
MRC Translational Immune Discovery Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
Background/objectives: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the and gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas.
View Article and Find Full Text PDFGenome Med
November 2024
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Nat Genet
December 2024
Institute of Health Informatics, University College London, London, UK.
PLoS Comput Biol
November 2024
Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
The ability to predict HIV-1 resistance to broadly neutralizing antibodies (bnAbs) will increase bnAb therapeutic benefits. Machine learning is a powerful approach for such prediction. One challenge is that some HIV-1 subtypes in currently available training datasets are underrepresented, which likely affects models' generalizability across subtypes.
View Article and Find Full Text PDFBrain Commun
November 2024
Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London EC1M 6BQ, UK.
Lower lung function is associated with lower cognitive function and an increased risk of dementia. This has not been adequately explained and may partly reflect shared developmental pathways. In UK Biobank participants of European ancestry, we tested the association between lung function measures (forced vital capacity and forced expiratory volume in 1 s to forced vital capacity ratio; = 306 476) and cognitive traits including nine cognitive function test scores ( = 32 321-428 609), all-cause dementia, Alzheimer's disease and vascular dementia (6805, 2859 and 1544 cases, respectively, and ∼421 241 controls).
View Article and Find Full Text PDFAnimals (Basel)
October 2024
Istituto Zooprofilattico Sperimentale della Sardegna, 07100 Sassari, Italy.
Canine distemper virus (CDV) is the etiological agent of a highly prevalent viral infectious disease of carnivores, which could seriously lead to a threat to the conservation of the affected species worldwide [...
View Article and Find Full Text PDFBJC Rep
January 2024
Biomedical Research Group, Department of Biomedical and Forensic Sciences, Faculty of Science and Technology, Anglia Ruskin University, Cambridge, CB1 1PT, UK.
Background: Transglutaminase 2 (TGM2) is a protein expressed in several isoforms in both intra- and extra-cellular tissue compartments. It has multiple functions that are important in cancer biology and several small studies have suggested expression of TGM2 in breast cancers is associated with a poorer prognosis. The aim of this study was to evaluate the role of intra-cellular and extra-cellular TGM2 expression in breast cancer and to determine whether there were any differences by hormone receptor status.
View Article and Find Full Text PDFNat Commun
November 2024
School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Queensland (QLD), Australia.
Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.
View Article and Find Full Text PDFJ Alzheimers Dis
November 2024
Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
Background: Bilateral oophorectomy (BO) confers immediate estradiol loss. We examined prevalence and predictors of Alzheimer's disease (AD) in women with early BO comparing their odds ratios of AD to those of women with spontaneous menopause (SM).
Methods: A cohort from UK Biobank (n = 34,603) included women aged 60 + at baseline with and without AD who had early BO or SM.
Nature
October 2024
Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
Loss-of-function mutations in the tumour suppressor APC are an initial step in intestinal tumorigenesis. APC-mutant intestinal stem cells outcompete their wild-type neighbours through the secretion of Wnt antagonists, which accelerates the fixation and subsequent rapid clonal expansion of mutants. Reports of polyclonal intestinal tumours in human patients and mouse models appear at odds with this process.
View Article and Find Full Text PDFCell
November 2024
Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, CO 80045, USA; Department of Structural Biology and Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. Electronic address:
STAR Protoc
December 2024
Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK; Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK. Electronic address:
The NLRP3 inflammasome is a key multi-protein complex controlling inflammation, particularly interleukin-1β (IL-1β) production. Here, we present a protocol to profile spatially resolved NLRP3 inflammasome complexes using ascorbic peroxidase 2 (APEX2)-based proximity labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). We describe steps for design and generation of the fusion construct, characterization of the stable FLAG-NLRP3-APEX2 expression cell line by western blotting/imaging, biotinylated proteome enrichment, and mass spectrometry analysis.
View Article and Find Full Text PDFLancet Digit Health
November 2024
Department of Statistics, University of Oxford, Oxford, UK; College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, UK. Electronic address:
Background: Understanding underlying mechanisms of heterogeneity in test-seeking and reporting behaviour during an infectious disease outbreak can help to protect vulnerable populations and guide equity-driven interventions. The COVID-19 pandemic probably exerted different stresses on individuals in different sociodemographic groups and ensuring fair access to and usage of COVID-19 tests was a crucial element of England's testing programme. We aimed to investigate the relationship between sociodemographic factors and COVID-19 testing behaviours in England during the COVID-19 pandemic.
View Article and Find Full Text PDFCell Rep
November 2024
Division of Mechanisms Regulating Gene Expression, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address:
The serine-/arginine-rich splicing factor 2 (SRSF2) plays pivotal roles in pre-mRNA processing and gene transcription. Recurrent mutations, particularly a proline-to-histidine substitution at position 95 (P95H), are common in neoplastic diseases. Here, we assess SRSF2's diverse functions in squamous cell carcinoma.
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